Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: An autoradiographic study

Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: An autoradiographic study
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富含多巴胺的纹状体内植入物可逆转大鼠黑质纹状体通路 6-羟基多巴胺损伤引起的多巴胺 D2 受体密度变化:一项放射自显影研究

DOI:
10.1016/0306-4522(92)90159-y
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发表时间:
1992
期刊:
影响因子:
3.3
通讯作者:
J. Herman
J. Herman
中科院分区:
医学3区
文献类型:
--
作者:
M. Savasta;F. Mennicken;M. Chritin;D. Abrous;C. Feuerstein;M. Moal;J. Herman

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本研究的目的是测试纹状体内植入胚胎多巴胺能神经元是否能够使损伤引起的纹状体多巴胺能受体的超敏反应正常化。用6-羟基多巴胺单侧损伤成年大鼠多巴胺上行通路。三周后,将ed14大鼠胚胎中脑细胞悬液植入去神经纹状体。植入后5个月测试对多巴胺能激动剂的旋转反应。1个月后处死动物,用放射自显影法定量纹状体多巴胺能受体密度,用标记多巴胺摄取位点的配体[3H]GBR 12935观察宿主纹状体的多巴胺能再神经支配。病变诱导了对多巴胺能激动剂的行为超敏反应,受损动物在接受多巴胺激动剂化合物SKF 38393 (2.5 mg/kg)或多巴胺激动剂LY 171555 (0.15 mg/kg)的试验剂量时,对病变的对侧表现出强烈的旋转。这些反应被移植物完全消除。d1和d2多巴胺能受体在大鼠纹状体中的正态分布与前面描述的相似。黑质纹状体多巴胺能通路损伤7个月后,d1受体密度未受明显影响,而d2受体密度增加约25-50%。胚胎多巴胺能神经元植入失神经纹状体后,d1受体密度略有下降,6个月后纹状体多巴胺能d2受体的增加发生逆转。此外,这种逆转不仅涉及再神经纹状体区域,而且延伸到非再神经纹状体区域。由此可见,胚胎多巴胺能神经元移植可使多巴胺能d2受体的密度恢复正常。
The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced hypersensitivity of striatal dopaminergic receptors. The ascending dopaminergic pathway of adult rats was unilaterally lesioned using 6-hydroxy-dopamine. Three weeks later a cell suspension obtained from the mesencephali of ED 14 rat embryos was implanted into the denervated striatum. Rotational responses to dopaminergic agonists were tested five months after implantation. One month later animals were killed and striatal dopaminergic receptor densities were quantified using autoradiography, the dopaminergic reinnervation of the host striatum being visualized with [3H]GBR 12935, a ligand labelling dopamine uptake sites. The lesion induced a behavioural hypersensitivity to dopaminergic agonists and lesioned animals displayed a strong rotation contralateral to the lesion in response to a test dose of the D1agonist compound SKF 38393 (2.5 mg/kg) or of the D2agonist LY 171555 (0.15 mg/kg). These responses were completely abolished by the graft. The normal distribution of D1and D2dopaminergic receptors in the rat striatum was similar to that described previously. Seven months after the lesion of the nigrostriatal dopaminergic pathway, the density of D1receptors was not significantly affected while the density of D2receptors was increased by about 25–50%. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a slight decrease of D1receptor densities and to a reversal of the lesion-induced increase of striatal dopaminergic D2receptors six months later. Moreover, this reversal concerned not only the reinnervated striatal region but also extended into non-reinnervated areas of the striatum.It is concluded that grafts of embryonic dopaminergic neurons can normalize the density of dopaminergic D2receptors.
大鼠大脑中多巴胺转运复合物的定量放射自显影定位:使用高选择性放射性配体:[3H]GBR 12935。
DOI: 10.1016/0014-2999(86)90757-0
发表时间: 1986
影响因子: 5
作者:
Dawson,TM;Gehlert,DR;Wamsley,JK
通讯作者: Wamsley,JK
通过黑质同源移植物使去神经大鼠纹状体中的螺哌啶醇结合正常化。
DOI: 10.1126/science.6635666
发表时间: 1983
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Freed,WJ;Ko,GN;Niehoff,DL;Kuhar,MJ;Hoffer,BJ;Olson,L;Cannon-Spoor,HE;Morihisa,JM;Wyatt,RJ
通讯作者: Wyatt,RJ